Sf Genome Data Analysis Meeting Final R

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Slide deck presented at 2012 whole genome data analysis summit.

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  • Prevalence of mental illness (NIMH 2009):Eating disorders 1-3% of population (includes three basic types: anorexia nervosa, bulimia nervosa and binge-eating disorder). 90% female. While it’s not a highly prevalent disorder, it is deadly. Over a decade, the mortality rate for people with anorexia is 5.6% which is about 12 times higher than the annual death rate due to all causes of death among females age 15-24. PTSD: 3.5% or 7.7 M AmericansADHD: one of most common disorders in children and adolescents also affect 4.1% adults in a given yearMood Disorders include all forms of depression and bipolar disorder 9.5% or 20.9 million adults in a given year have a mood disorderAnxiety Disorders: include panic disorder, general anxiety disorder, OCD,phobias 33 million peopleFor comparisonAll forms of Cancer 3.7% or 11 millionDiabetes 8% or 23.5 million Statistics from the American Heart Association Estimates for the year 2006 gave the breakdown for that year as follows - In 2006, among those who had heart disease, approximately 73.6 million suffered from high blood pressure, 16.8 million had coronary artery disease (i.e. had experienced an acute heart attack or had active angina or chest pain), 6.5 million had dealt with a stroke, and 5.7 million had experienced heart failure.  American Cancer FoundationAmerican Diabetes AssociationAmerican Heart Association
  • Prevalence of mental illness (NIMH 2009):Eating disorders 1-3% of population (includes three basic types: anorexia nervosa, bulimia nervosa and binge-eating disorder). 90% female. While it’s not a highly prevalent disorder, it is deadly. Over a decade, the mortality rate for people with anorexia is 5.6% which is about 12 times higher than the annual death rate due to all causes of death among females age 15-24. PTSD: 3.5% or 7.7 M AmericansADHD: one of most common disorders in children and adolescents also affect 4.1% adults in a given yearMood Disorders include all forms of depression and bipolar disorder 9.5% or 20.9 million adults in a given year have a mood disorderAnxiety Disorders: include panic disorder, general anxiety disorder, OCD,phobias 33 million peopleFor comparisonAll forms of Cancer 3.7% or 11 millionDiabetes 8% or 23.5 million Statistics from the American Heart Association Estimates for the year 2006 gave the breakdown for that year as follows - In 2006, among those who had heart disease, approximately 73.6 million suffered from high blood pressure, 16.8 million had coronary artery disease (i.e. had experienced an acute heart attack or had active angina or chest pain), 6.5 million had dealt with a stroke, and 5.7 million had experienced heart failure.  American Cancer FoundationAmerican Diabetes AssociationAmerican Heart Association
  • Sf Genome Data Analysis Meeting Final R

    1. 1. AssureRx Health, Inc. CONFIDENTIAL 1
    2. 2. Mayo Clinic and Cincinnati Children’s Hospital experience & technology • Mayo: Patent-pending technology • >5,000 patients genotyped • “Gene Team” expertise • Routine in clinical use• CCH: Patent-pendingtechnology• >7,000 patients genotyped• Standard-of-care• Genetic and non-genetic factors• Drug-drug interactions Privately-held with key investments from Claremont Creek Ventures, Sequoia Capital ventures, CincyTech and other investment groups.
    3. 3. AssureRx Health, Inc. CONFIDENTIAL 3
    4. 4. Lifetime prevalence of psychiatric illnesses Eating Disorders 1-3% PTSD 3.5% ADHD 4.1 % Mood Disorders 9.5% Anxiety Disorders 15% Cancer (All) 3.7%Coronary Heart Disease 5.6% Diabetes 8% 0 5 10 1 20 5 Percentage of US Population Two-fold greater aggregate prevalence of psychiatric illness vs cancer, cardiovascular, or metabolic disorders (NIMH, 2009; Am. Cancer Society 2006; Am. Diabetes Assn, 2008; Am. Heart Assn, 2006, Lindner Center of Hope, Cincinnati, OH).
    5. 5. CYP450 Metabolizer PhenotypesULTRA-RAPID: Increased expression of a metabolizingenzyme, and will metabolize a drug at a rapid rate.EXTENSIVE: Wild type or “normal” phenotype,in some cases.INTERMEDIATE: An individual who possesses one semi-functional or non-functional allelePOOR: An individual with decreased or no expressionof a metabolizing enzyme, and metabolize a drug veryslowly or not at all.
    6. 6. 19 Antidepressants in a Pharmacogenomic support algorithm 5HT2A Antagonist/SSRI (SARI)Selective Serotonin Reuptake Blockers (SSRI) Nefazodone (Serzone®)Citalopram (Celexa®) Trazodone (Desyrel®)Fluoxetine (Prozac®) Trazodone ER (Oleptro®)Escitalopram (Lexapro®)Fluvoxamine (Luvox®) Tricyclic (TCA)Paroxetine (Paxil®) Imipramine (Tofranil®)Sertraline (Zoloft®) Desipramine (Norpramin®) Amitriptyline (Evavil®)SSRI/5HT-1A partial agonist Nortriptyline (Pamelor®)Vilazadone (Viibryd®) Clomipramine (Anafranil ®)Aripiprazole (Abilify®) (D2/1A partial agonist) Doxepin (Sinequan®) Protriptyline (Vivactil®)Norepineprhine-Dopamine Reuptake Blockers (NDRI) Trimipramine (Surmontil®)Bupropion (& SR, XL (Wellbutrin® or Zyban®)Bupropion Hydrobromide (Aplenzin®) Tetracyclic Maprotiline (Ludiomil®)Serotonin-Norepineprhine Reuptake Blockers (SNRI) Amoxapine (Asendin®)Venlafaxine (Effexor XR®)Desvenlafaxine (Pristiq®) Irreversible MAO-A/B InhbitorsDuloxetine (Cymbalta®) Isocarboxazid (Marplan®) Phenelzine (Nardil®)Noradrenergic/Specific Serotonergic (NaSSA) Tranylcypromine (Parnate®)Mirtazepine (Remeron®) Selegiline (Emsam® patch; MAOB)
    7. 7. Using the GeneSightRx® treatment-support solution for medication selectione-Test ordered Web-based patient report Proprietary AlgorithmPGx Sample Clinical Laboratory Improvement Amendments (CLIA) compliant College of American Pathologists (CAP) accredited Certified by the New York Department of Health
    8. 8. GeneSightRx® Psychotropic TestGenotype Phenotype Interpretive Drug Medication Sorting BinningCYP2D6 Metabolizer Status Use as DirectedCYP2C19 Metabolizer StatusCYP2C9 Metabolizer Status Effect of Composite Use with Phenotype onCYP1A2 Metabolizer Status Caution Each DrugSLC6A4 Transporter Activity Use with Caution and5HTR2A Receptor Activity More Frequent Monitoring 1. The patient’s genotype is determined for each gene in the panel 2. A phenotype is predicted for each genotype 3. A composite phenotype for each drug is created based on all 6 phenotypes 4. The 19 most commonly prescribed antidepressants and 13 antipsychotics are positioned in a green, yellow, or red “bin”.
    9. 9. Sample Patient ReportGeneSightRx Psychotropics
    10. 10. Meta-analysis: GeneSightRx improves 8 week antidepressant responseA meta-analysis of 3 independent, prospective, controlled studies of GeneSightRx-managed patients shows a 28% reduction in the rate of failure among patients whohad previously failed pharmacotherapy for MDD.
    11. 11. Cost benefits of improving therapeutic response with GeneSightRx® Direct medical costs and productivity costs Fail toAnnual MDD costs per patient Respond respondAnnual direct medical costs per patient $12,155 $5,755 Pharmacy - Depression drug costs $1,246 $429 Inpatient $2,600 $1,283 Outpatient Physician $6,053 $1,913 Other $2,256 $2,130Employer productivity costs $4,973 $1,015 Productivity $504 $278 Absenteeism $4,469 $737Annual medical & productivity cost/pt $17,128 $6,770Comparisons of TAU and GeneSightRx TAU GSRxFailure to respond rate 79% 51%Response rate 21% 47%
    12. 12. ConclusionsProspective, randomized double-blind clinical trials show thatGeneSightRx® improves antidepressant efficacy compared topatients who receive treatment as usual (TAU).Efficacy improvement is greatest for patients on multiplemedications (likely to be treatment-resistant), and thoseidentified by the test to be taking problematic, red-binneddrugs (data not shown).GeneSightRx® is a rapid and effective pharmacogenomicdecision support tool, and can be used for cohort stratificationprior to clinical trials.
    13. 13. AssureRx Health, Inc. CONFIDENTIAL 13
    14. 14. Demogenics of 17,131 human genome sequencesAssureRx Health, Inc. CONFIDENTIAL 14
    15. 15. How do we process all of these sequences?Data production Data storage, manipulation Data annotation, interpretation Report generation
    16. 16. AssureRx Health, Inc. CONFIDENTIAL 16
    17. 17. Lee Hood, IOM February 27, 2012
    18. 18. Trends in NGS and Drug Development1. Precompetitive data sharing using collaborative informatics: • tranSMART • TransCelerate BioPharma2. Nanopore-based, single molecule sequencing.1. Improved understanding of human variation of all types– “it isnt just the SNPs anymore.”AssureRx Health, Inc. CONFIDENTIAL 18
    19. 19. Applications in Drug Discovery“The ideal nucleic acid sequencing technology for drug discoveryand development should:• Sequence natural DNA/RNA fragments of various sizes fully with minimal (or no) errors• Haplotype phasing on a chromosome scale;• Generate no sequence-dependent or other biases;• Require minimum quantities of input material, ideally single cells;• Have high/complete efficiency in all of the sequencing steps;• Detect modified nucleotides (such as methylated cytosines) directly;• Operate in laboratories and low-resource settings without special external environment requirements such as temperature and humidity control.” – Mike Braxenthaler, Roche and Pistoia Alliance AssureRx Health, Inc. CONFIDENTIAL 19
    20. 20. The Biggest Problem we can’t solve Potential for Drug-Drug Interactions! Number of Patients Aged 18-24 / VA Med. Ctr. Average number of prescription drugs per day 3,125 5,860 6,001 12, 392 average average average average number of number of number of number of drugs each drugs each drugs each drugs each day =19 day = 15 day = 12 day = 7AssureRx Health, Inc. CONFIDENTIAL 20

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